INITIAL INSIGHTS INTO THE STRUCTURE-ACTIVITY RELATIONSHIPS OF AVIAN DEFENSINS.
(2011) In Journal of Biological Chemistry- Abstract
- Numerous β-defensins have been identified in birds and the potential use of these peptides as alternatives to antibiotics has been proposed, in particular to fight antibiotic-resistant and zoonotic bacterial species. Little is known about the mechanism of antibacterial activity of avian β-defensins (AvBDs), and the present work was carried out to obtain initial insights into the involvement of structural features or specific residues in the antimicrobial activity of chicken AvBD2. Chicken AvBD2 and its enantiomeric counterpart were chemically synthesized. Peptide elongation and oxidative folding were both optimized. The similar antimicrobial activity measured for both L- and D- proteins clearly indicates that there is no chiral partner.... (More)
- Numerous β-defensins have been identified in birds and the potential use of these peptides as alternatives to antibiotics has been proposed, in particular to fight antibiotic-resistant and zoonotic bacterial species. Little is known about the mechanism of antibacterial activity of avian β-defensins (AvBDs), and the present work was carried out to obtain initial insights into the involvement of structural features or specific residues in the antimicrobial activity of chicken AvBD2. Chicken AvBD2 and its enantiomeric counterpart were chemically synthesized. Peptide elongation and oxidative folding were both optimized. The similar antimicrobial activity measured for both L- and D- proteins clearly indicates that there is no chiral partner. Therefore the bacterial membrane is in all likelihood the primary target. Moreover, this work evidences that the three-dimensional fold is required for an optimal antimicrobial activity, in particular for Gram-positive bacterial strains. The three-dimensional NMR structure of chicken AvBD2 defensin displays the structural 3-stranded antiparallel β-sheet characteristic of β-defensins. The surface of the molecule does not display any amphipathic character. In light of this new structure and of the king penguin AvBD103b defensin structure, the consensus sequence of avian β-defensin's family was analyzed. Well conserved residues were highlighted and the potential strategic role of the lysine 31 residue of AvBD2 emphasized. The synthetic AvBD2-K31A variant displayed substantial N-terminal structural modifications and a dramatic decrease in activity. Taken together, these results demonstrate the structural as well as the functional role of the critical lysine 31 residue in antimicrobial activity. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2273476
- author
- Derache, Chrystelle LU ; Meudal, Herve ; Aucagne, Vincent ; Mark, Kevin J ; Cadene, Martine ; Delmas, Agnes F ; Lalmanach, Anne-Christine and Landon, Celine
- organization
- publishing date
- 2011-12-27
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:22205704
- scopus:84857712974
- pmid:22205704
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M111.312108
- language
- English
- LU publication?
- yes
- id
- 969ff348-ad29-4f38-babd-9d29c86cbcec (old id 2273476)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22205704?dopt=Abstract
- date added to LUP
- 2016-04-01 09:58:03
- date last changed
- 2022-04-19 21:26:26
@article{969ff348-ad29-4f38-babd-9d29c86cbcec,
abstract = {{Numerous β-defensins have been identified in birds and the potential use of these peptides as alternatives to antibiotics has been proposed, in particular to fight antibiotic-resistant and zoonotic bacterial species. Little is known about the mechanism of antibacterial activity of avian β-defensins (AvBDs), and the present work was carried out to obtain initial insights into the involvement of structural features or specific residues in the antimicrobial activity of chicken AvBD2. Chicken AvBD2 and its enantiomeric counterpart were chemically synthesized. Peptide elongation and oxidative folding were both optimized. The similar antimicrobial activity measured for both L- and D- proteins clearly indicates that there is no chiral partner. Therefore the bacterial membrane is in all likelihood the primary target. Moreover, this work evidences that the three-dimensional fold is required for an optimal antimicrobial activity, in particular for Gram-positive bacterial strains. The three-dimensional NMR structure of chicken AvBD2 defensin displays the structural 3-stranded antiparallel β-sheet characteristic of β-defensins. The surface of the molecule does not display any amphipathic character. In light of this new structure and of the king penguin AvBD103b defensin structure, the consensus sequence of avian β-defensin's family was analyzed. Well conserved residues were highlighted and the potential strategic role of the lysine 31 residue of AvBD2 emphasized. The synthetic AvBD2-K31A variant displayed substantial N-terminal structural modifications and a dramatic decrease in activity. Taken together, these results demonstrate the structural as well as the functional role of the critical lysine 31 residue in antimicrobial activity.}},
author = {{Derache, Chrystelle and Meudal, Herve and Aucagne, Vincent and Mark, Kevin J and Cadene, Martine and Delmas, Agnes F and Lalmanach, Anne-Christine and Landon, Celine}},
issn = {{1083-351X}},
language = {{eng}},
month = {{12}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{INITIAL INSIGHTS INTO THE STRUCTURE-ACTIVITY RELATIONSHIPS OF AVIAN DEFENSINS.}},
url = {{https://lup.lub.lu.se/search/files/1432446/2374056.pdf}},
doi = {{10.1074/jbc.M111.312108}},
year = {{2011}},
}